The object of this proposal is to investigate the nature of the immunologic processes involved in autoimmune and viral-induced experimental demyelinating diseases. Autoimmune demyelination will be elicited by myelin basic protein; in the viral-induced models, demyelination will be elicited by infection with parainfluenza, mouse hepatitis or murine encephalomyelitis virus. Interest in these models centers on their usefulness in examine the hypothesis that the human demyelinating syndrome, multiple sclerosis (MS) is due to the immune response of a genetically susceptible host to one or more viral infections of the central nervous system. The goal of this project is to apply relevant information acquired in the study of experimental models to diagnosis and treatment of human disease. Various immunologic parameters will be compared between the two models and, when feasible with MS. The role of genetic factors in determining susceptibility and resistance, which appear prominent in MS, will be examined in inbred strains of mice with autoimmune and virus-associated encephalomyelitis. The contribution of T and B lymphocytes to disease development and modulation will be ascertained by adoptively transferring purified cell populations. The nature of the antigen(s) that elicits antibody which inhibits myelination in nervous tissue cultures remains to be identified; it is a unique link between the autoimmune model in animals and MS. The possible presence of a myelin inhibitory antibody in virus-associated demyelination could lend additional support for the validity of this model. Recent technical improvements using insoluble radiolabeled immunoglobulins make it feasible to develop a sensitive test to detect myelin breakdown components in the spinal fluid or serum of primates with autoimmune encephalitis. (These specimens are available from our previous studies.) The detection of early myelin loss could provide a powerful diagnostic tool in MS.